HUbiquitome: a database of experimentally verified ubiquitination cascades in humans

Abstract

Protein ubiquitination is an evolutionarily conserved and functionally diverse post-translational modification achieved through the sequential action of E1-activating enzymes, E2-conjugating enzymes and E3 ligases. A summary of validated ubiquitination substrates have been presented and a prediction of new substrates have been conducted in yeast. However, a systematic summary of human ubiquitination substrates containing experimental evidence and the enzymatic cascade of each substrate is not available. In the present study, hUbiquitome web resource is introduced, a public resource for the retrieval of experimentally verified human ubiquitination enzymes and substrates. hUbiquitome is the first comprehensive database of human ubiquitination cascades. Currently, hUbiquitome has in its repertoire curated data comprising 1 E1 enzyme, 12 E2 enzymes, 138 E3 ligases or complexes, 279 different substrate proteins and 17 deubiquitination enzyme terms. The biological functions of substrates from different kinds of E3s were analyzed using the collected data. The findings show that substrates ubiquitinated by RING (Really Interesting New Gene) E3s are enriched most in apoptosis-related processes, whereas substrates ubiquitinated by other E3s are enriched in gene expression-associated processes. An analysis of the data demonstrates the biological process preferences of the different kinds of E3s. hUbiquitome is the first database to systematically collect experimentally validated ubiquitinated proteins and related ubiquitination cascade enzymes which might be helpful in the field of ubiquitination-modification research.Database URL: http://202.38.126.151/hmdd/hubi/